Comparison of human skin irritation and photo-irritation patch test data with cellular in vitro assays and animal in vivo data

Replacement of the rabbit Draize skin irritation test or the animal photo-irritation test is in course in Europeunder the REACH chemical strategy and the Cosmetics Directive. Various in vitro protocols, including3D skin models, have been assessed. One key difficulty in determining the validity of alternative in vitromethods is that the in vivo animal data is both scarce and often of limited utility for prediction of effectsin man. Consequently, we have examined in human 4h patch tests a number of chemicals of EU borderlineclassification. In addition, in a specific group of cosmetic ingredients we assessed the potential of photoirritationusing results obtained in 3D skin models and in human photopatch tests. Several chemicals reportedto be irritant in the rabbit were found to be without effect in humans. 3D skin model assays and human patchtests provided concordant results particularly in case of non-irritating and non-phototoxic substances. In ourview, skin model tests seem to be a useful tool for the prediction of human skin irritation or phototoxicityhazard, particularly for consideration of initial concentration for confirmatory human patch tests to provesubstance and product safety.